Berries and Cancer Prevention

1. Auflage 2010
ISBN: 978-1-4419-7554-6
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 313 Seiten

Experimental investigations in the past 10-15 years have provided convincing evidence of the cancer preventive potential of berries. Berries and their components have been shown to reduce the malignant properties of cancer cells in culture by influencing genes associated with cancer development. In addition, diets containing freeze-dried berries have been shown to prevent cancer in animals, and recent data indicate that they also exhibit cancer preventive effects in humans.

Autoren/Hrsg.

Inhaltsverzeichnis

1;Preface;4
2;Contents;5
3;Contributors;7
4;Part I Berry Composition, Bioavailability, Metabolism and Biological Effects;10
4.1;1 Contribution of Berry Anthocyanins to Their Chemopreventive Properties;11
4.1.1;1 Introduction;11
4.1.2;2 Incidence of Anthocyanins in Berries;12
4.1.2.1;2.1 Types of Anthocyanins Found in Berries;12
4.1.2.2;2.2 Anthocyanin Concentration in Berries;18
4.1.3;3 Anthocyanin Chemoprotective Effects: In Vitro Studies;18
4.1.3.1;3.1 Antioxidative Activity;29
4.1.3.2;3.2 Detoxification Activity;29
4.1.3.3;3.3 Antiproliferation;30
4.1.3.4;3.4 Apoptosis Induction;31
4.1.3.5;3.5 Anti-inflammatory Effects;32
4.1.3.6;3.6 Anti-angiogenic Activity;32
4.1.3.7;3.7 Anti-invasiveness;33
4.1.4;4 In Vivo Chemoprotective Studies;33
4.1.4.1;4.1 Animal Studies;33
4.1.4.1.1;4.1.1 Colon Cancer;33
4.1.4.1.2;4.1.2 Esophageal Cancer;34
4.1.4.1.3;4.1.3 Other Cancers;34
4.1.4.2;4.2 Human Studies;35
4.1.5;5 Impact of Anthocyanin Chemical Structure on Their Chemoprotective Properties;36
4.1.6;6 Interaction Effects of Anthocyanins with Other Phytochemicals in Berries;38
4.1.7;7 Bioavailability;38
4.1.8;References;41
4.2;2 Ursolic Acid and Other Pentacyclic Triterpenoids: Anticancer Activities and Occurrence in Berries;49
4.2.1;1 Introduction;49
4.2.2;2 Occurrence of Ursolic Acid and Other Triterpenoids in Vaccinium Berries;50
4.2.3;3 Triterpenoids in Other Berries;52
4.2.4;4 Anti-cancer and Anti-inflammatory Activities of Ursolic Acid and Its Esters;53
4.2.5;5 Mechanisms of Action;54
4.2.6;6 Future Research Directions;55
4.2.7;References;55
4.3;3 The Effects of Berry Extracts on Cell Signaling Pathways: Leading to Cellular Transformation;58
4.3.1;1 Introduction;60
4.3.2;2 Receptor Tyrosine Kinases (RTKs);60
4.3.2.1;2.1 RTK Signaling Pathways and Cancers;60
4.3.2.2;2.2 The Effects of Berry Extracts on RTK Pathways and Their Chemoprevention;62
4.3.3;3 PI3K/Akt Signaling Pathway;63
4.3.3.1;3.1 PI3K/Akt Signaling Pathway and Cancer;63
4.3.3.2;3.2 The Effects of Berry Extracts on PI3K/Akt Pathway and Their Chemoprevention;65
4.3.4;4 Mitogen-Activated Protein Kinases (MAPKs);66
4.3.4.1;4.1 MAPK Signaling Pathways and Cancers;66
4.3.4.2;4.2 The Effects of Berry Extracts on MAPK Pathways and Their Role in Chemoprevention;69
4.3.5;5 Transcription Factors and Their Downstream Target Genes;69
4.3.5.1;5.1 The Role of NF B, AP-1, COX-2, and VEGF in Cancers;69
4.3.5.2;5.2 The Effects of Berry Extracts on Activation of NF B and AP-1, and Expression of COX-2 and VEGF;71
4.3.6;6 Conclusion;73
4.3.7;References;74
5;Part II Antioxidant Capacity of Berry Components;83
5.1;4 Correlation of Antioxidants and Antioxidant Enzymes to Oxygen Radical Scavenging Activities in Berries;84
5.1.1;1 Introduction;84
5.1.2;2 Correlation Related to Species and Genotype Variation;85
5.1.3;3 Correlation Related to Specific Tissues;88
5.1.4;4 Correlation Affected by Maturation;89
5.1.5;5 Correlation Affected by Preharvest Conditions;91
5.1.5.1;5.1 Environmental Conditions;91
5.1.5.2;5.2 Cultural Practices;91
5.1.6;6 Correlation Affected by Postharvest Handling;92
5.1.6.1;6.1 Storage Conditions;92
5.1.6.2;6.2 Controlled Atmospheres;93
5.1.6.3;6.3 Heat Treatment;94
5.1.6.4;6.4 Illumination;95
5.1.6.5;6.5 Ozone;96
5.1.6.6;6.6 Treatment with Naturally Occurring Compounds;96
5.1.6.6.1;6.6.1 Methyl Jasmonate;97
5.1.6.6.2;6.6.2 Essential Oils and Other Natural Volatile Compounds;97
5.1.7;7 Conclusion;98
5.1.8;References;98
6;Part III Chemopreventive Effects of Berries and Berry Components in Animal Model Systems;103
6.1;5 Berries in the Prevention of Esophageal Adenocarcinoma;104
6.1.1;1 Esophageal Adenocarcinoma and Related Precursor Lesions;105
6.1.1.1;1.1 Epidemiology of Barrett's Esophagus and Esophageal Adenocarcinoma;105
6.1.1.1.1;1.1.1 Obesity as a Risk Factor;105
6.1.1.1.2;1.1.2 Tobacco and Alcohol as EAC Risk Factors;106
6.1.1.1.3;1.1.3 Dietary Factors and Supplementation Relative to EAC Risk;106
6.1.1.1.4;1.1.4 Additional Risk Factors for EAC;107
6.1.1.1.5;1.1.5 Summary of Molecular Alterations;108
6.1.2;2 Methodological Challenges;109
6.1.2.1;2.1 Preclinical Assessments Utilizing Animal Models and In Vitro Systems;109
6.1.3;3 Berries as Chemopreventive Agents Targeting BE or EAC;113
6.1.4;References;114
6.2;6 Endothelial Cell Tumor Prevention with Berry Extracts: Clinical Problems, Molecular Mechanisms and Therapeutic Opportunities;119
6.2.1;1 Endothelial Cell Tumors: The Clinical Problem;119
6.2.1.1;1.1 Incidence;119
6.2.1.2;1.2 Indications for Treatment;120
6.2.1.3;1.3 Current Treatment Options;121
6.2.1.4;1.4 Experimental Models of Endothelial Cell Tumors;121
6.2.2;2 Molecular Mechanisms Oxidant Production Promotes Endothelial Cell Tumor Growth;122
6.2.2.1;2.1 Contribution of Nox-4 Derived Oxidants;122
6.2.2.2;2.2 The Role of AP-1 and NF-kB;123
6.2.2.3;2.3 MCP-1 Is Required for Endothelial Cell Tumor Formation;124
6.2.3;3 Therapeutic Opportunities Using Blueberry Extract;125
6.2.3.1;3.1 Oxidant Derived Biomarkers to Monitor Response to Treatment;125
6.2.3.2;3.2 Effects of BBE on Pro-tumorigenic Responses In Vitro;126
6.2.3.3;3.3 Effects of BBE Treatment on Endothelial Cell Tumor Growth In Vivo;126
6.2.4;4 Summary;127
6.2.5;References;128
6.3;7 Effects of Black Raspberries on UV-Induced Cutaneous Inflammation and Tumor Development;133
6.3.1;1 The Skin;134
6.3.1.1;1.1 Structure/Function;134
6.3.1.2;1.2 Malignancies;134
6.3.1.2.1;1.2.1 Susceptible Populations;135
6.3.2;2 Ultraviolet Light;135
6.3.2.1;2.1 Wavelengths;135
6.3.2.2;2.2 Role in Cutaneous Inflammation and Carcinogenesis;136
6.3.2.3;2.3 Murine Models of UV Induced Inflammation and Skin Cancer;137
6.3.3;3 Black Raspberries;137
6.3.3.1;3.1 Background;137
6.3.3.2;3.2 Role as Chemopreventive/Chemotherapeutic Agents in Skin;138
6.3.4;4 Conclusion;139
6.3.5;References;140
6.4;8 Chemopreventive Effects of Berries and Berry Components in the Rodent Esophagus;145
6.4.1;1 Introduction;146
6.4.1.1;1.1 Esophageal Cancer;146
6.4.1.2;1.2 Rat Model of Esophageal Squamous Cell Carcinoma;146
6.4.1.2.1;1.2.1 Metabolism of NMBA;146
6.4.2;2 Chemoprevention of Esophageal Cancer in Rats;147
6.4.2.1;2.1 Chemoprevention Protocols;147
6.4.2.2;2.2 Black Raspberries;150
6.4.2.3;2.3 Berries Inhibit Initiating Events in NMBA-Treated Rat Esophagus;151
6.4.2.3.1;2.3.1 Effects on DNA Adduct Formation;151
6.4.2.3.2;2.3.2 Effects on Cytochrome P450 Enzymes;151
6.4.2.3.3;2.3.3 Potential Effects on H-ras Oncogene Activation;152
6.4.2.3.4;2.3.4 Effects on Gene Expression as Determined by DNA Microarray;152
6.4.2.4;2.4 Effects of BRBs on Preneoplastic Lesions and Papilloma Formation;153
6.4.2.5;2.5 Berries Inhibit Post-initiation Events in Rat Esophageal Carcinogenesis;155
6.4.2.5.1;2.5.1 Effects on Genes Associated with Inflammation;155
6.4.2.5.2;2.5.2 Effects on Genes Associated with Cell Proliferation and Cell Cycle Progression;155
6.4.2.5.3;2.5.3 Effects on Genes Associated with Apoptosis and Cell Differentiation;156
6.4.2.5.4;2.5.4 Effects on Genes Associated with Angiogenesis;156
6.4.3;3 Identification of Bioactive Agents in Berries for Prevention of Esophageal Cancer in Rats;157
6.4.4;4 Other Berry Types Also Prevent Esophageal Tumorigenesis in Rats;159
6.4.5;References;162
6.5;9 Chemopreventive Effects of Berries and Berry Components in Animal Models: Prevention of Estrogen-Mediated Mammary Tumors in ACI Rats by Berries;164
6.5.1;1 Introduction;165
6.5.1.1;1.1 Breast Cancer Risk Factors and Prevention;165
6.5.1.2;1.2 Estrogen-Induced Mammary Tumors in ACI Rats;167
6.5.1.3;1.3 Berries in the Prevention of Estrogen-Mediated Mammary Tumorigenesis;171
6.5.1.4;1.4 Prevention of Mammary Tumorigenesis by Dietary Berries;175
6.5.1.5;1.5 Correlation Between Chemopreventive Potential and Anthocyanin Profiles of Blueberry and Black Raspberry;178
6.5.1.6;1.6 Translation to Community and Clinical Nutrition;179
6.5.1.7;References;182
6.6;10 Inhibition of Oral Cancer in Animal Models by Black Raspberries and Berry Components;189
6.6.1;1 Oral Cancer as a Site for Chemoprevention;190
6.6.1.1;1.1 Oral Cancer;190
6.6.1.2;1.2 Oral Cancer and Chemoprevention;191
6.6.1.3;1.3 Berry--Based Chemoprevention;191
6.6.2;2 Animal Models of Chemically-Induced Oral Cancer;192
6.6.2.1;2.1 Hamster Oral Carcinogenesis Model;192
6.6.2.2;2.2 Rat and Mouse Oral Carcinogenesis Models;193
6.6.3;3 Prevention of Oral Cancer by Black Raspberries;195
6.6.3.1;3.1 Complete Chemoprevention Bioassay with Dietary Administration of Black Raspberries;196
6.6.4;4 Prevention of Oral Cancer by Berry Components;197
6.6.4.1;4.1 Quercetin;198
6.6.4.2;4.2 Ferulic Acid;198
6.6.4.3;4.3 -carotene;199
6.6.4.4;4.4 Protocatechuic Acid;200
6.6.5;5 Summary and Discussion;201
6.6.6;References;201
6.7;11 Prevention of Cancer with Pomegranate and Pomegranate Anthocyanins;208
6.7.1;1 Pomegranates: An overview;208
6.7.2;2 Pomegranate Chemistry;209
6.7.3;3 Pomegranates and Cancer;210
6.7.3.1;3.1 Pomegranates and Skin Cancer;211
6.7.3.2;3.2 Pomegranate and Prostate Cancer;213
6.7.3.3;3.3 Pomegranate and Breast Cancer;217
6.7.3.4;3.4 Pomegranate and Colon Cancer;219
6.7.3.5;3.5 Pomegranate and Lung Cancer;220
6.7.4;4 Future Perspective and Conclusions;221
6.7.5;References;222
6.8;12 Chemoprevention of Chronic Inflammatory Bowel Disease-Induced Carcinogenesis in Rodent Models by Berries;226
6.8.1;1 Introduction;226
6.8.2;2 Molecular Pathogenesis and Modeling of Inflammatory Bowel Disease-Induced Carcinogenesis;228
6.8.3;3 The Protective Effects of Berries Against Colitis and Colitis-Induced Cancer: Epidemiologic and Experimental Evidence;230
6.8.3.1;3.1 Epidemiologic Studies;230
6.8.3.2;3.2 Experimental Studies;231
6.8.4;4 Key Active Components of Berries in Prevention of Colitis and Colitis-Induced Cancer in Rodent Models;233
6.8.4.1;4.1 Berry-Derived Fiber, Especially Fructooligosaccharides, as a Crucial Probiotic Against Colitis;233
6.8.4.2;4.2 Berry-Derived Anthocyanins as an Active Phytonutrient Against Inflammation and Carcinogenesis;234
6.8.5;5 Molecular Target or Mechanism of Berry and Its Extract on Inhibiting Inflammation and Carcinogenesis;235
6.8.5.1;5.1 Anti-Inflammation-Induced Nitro-Oxidative Stress;235
6.8.5.2;5.2 Inhibition of Aberrant Oxylipin Metabolic Profile;236
6.8.5.3;5.3 Modulation of Inflammation or Carcinogen-Activated Gene Expression Profile, Particularly Focusing on Inflammation and Cancer Signaling Including Apoptosis, Proliferation and Angiogenesis;237
6.8.6;6 Summary and Conclusion;238
6.8.7;References;239
7;Part IV Berry Chemoprevention in High-Risk Populations;243
7.1;13 Cancer Prevention in Humans at High-Risk for Development of Cancer: Prevention of Oral Dysplasia in Humans by Berry Formulations;244
7.1.1;References;253
7.2;14 Cancer Prevention in Populations High At-RiskINTnl; for the Development of Oral Cancer: Clinical TrialsINTnl; with Black Raspberries;256
7.2.1;1 Oral Cancer;257
7.2.1.1;1.1 Oral Cancer Background;257
7.2.1.2;1.2 Molecular Biology of Oral Cancer;259
7.2.1.3;1.3 Prevention of Oral Cancer by Whole Foods;260
7.2.1.4;1.4 Food-Based Phytochemicals and Cancer Prevention;262
7.2.1.5;1.5 Black Raspberries as a Cancer Prevention Agent;262
7.2.1.6;1.6 Pre-clinical Studies with Black Raspberries in Human Oral Cancer Cells;263
7.2.1.6.1;1.6.1 Black Raspberry Extract and Human Oral Cancer Cell Proliferation;263
7.2.1.6.2;1.6.2 Modulation of In Vitro Gene Expression Profiles Associated with Oral Carcinogenesis;264
7.2.1.7;1.7 Clinical Studies with Black Raspberries in Oral Cancer Patients;266
7.2.1.7.1;1.7.1 Phase I Clinical Trial: Pre-surgical Model;266
7.2.1.7.2;1.7.2 Phase I/II Clinical Trial: Post-surgical Model;270
7.2.1.8;1.8 Black Raspberries, Cancer Prevention, and Future Directions;273
7.2.1.9;References;274
7.3;15 Effects of Black Raspberries on Cellular and Epigenetic Biomarkers of Colon Cancer Development in Humans;278
7.3.1;1 Introduction;279
7.3.1.1;1.1 Colon Cancer;279
7.3.2;2 Molecular Basis of Colon Cancer;280
7.3.2.1;2.1 Chromosomal Instability;280
7.3.2.2;2.2 DNA-Repair Defects;280
7.3.2.3;2.3 Aberrant DNA Methylation;281
7.3.2.4;2.4 Mutational Activation of Oncogenes;281
7.3.2.5;2.5 Mutational Inactivation of Tumor Suppressor Genes;281
7.3.2.6;2.6 Other Molecular Events;283
7.3.3;3 Epidemiological Evidence for the Prevention of Colon Cancer with Berries;284
7.3.4;4 Preclinical Studies with BRBs and Colon Cancer;284
7.3.4.1;4.1 Cell Culture Studies;284
7.3.4.2;4.2 Animal Bioassays;285
7.3.5;5 Human Clinical Trials;285
7.3.5.1;5.1 Phase Ia Clinical Trial;285
7.3.5.2;5.2 Phase Ib Clinical Trial in Patients with Colorectal Cancer;286
7.3.5.2.1;5.2.1 Black Raspberry Powder;287
7.3.5.2.2;5.2.2 Patient Population and Clinical Trial Procedures;287
7.3.5.3;5.3 Laboratory Analyses;290
7.3.5.3.1;5.3.1 Measurement of Berry Anthocyanins in Colorectal Tissues and Urine;290
7.3.5.3.2;5.3.2 Analysis of DNA Methylation;290
7.3.5.3.3;5.3.3 Statistics;291
7.3.5.4;5.4 Results;291
7.3.5.4.1;5.4.1 Patient Characteristics;291
7.3.5.4.2;5.4.2 Berry Treatment and Compliance Data;293
7.3.5.4.3;5.4.3 Anthocyanins in Urine and Colorectal Tissue;293
7.3.5.4.4;5.4.4 BRBs Cause Promoter Demethylation of Tumor Suppressor Genes in Wnt Pathway;293
7.3.5.4.5;5.4.5 Wnt Signaling, Cell Proliferation, Apoptosis and Angiogenesis;295
7.3.6;6 Summary and Conclusions;298
7.3.7;References;298
8;Index;301